title: Distribution of platinum in blood and perilymph in relation to cisplatin induced ototoxicity in the guinea pig.
abstract: Cisplatin, a platinum-based chemotherapeutic drug, has severe dose-limiting side effects which include ototoxicity. In this study, we investigate the ototoxic effects of cisplatin in relation to the concentration of platinum in whole blood, plasma and perilymph. Guinea pigs were equipped with a permanent round window electrode for electrocochleography and treated with cisplatin on a daily basis (1.5mg/kg/day ip) until a 40dB shift of the compound action potential (CAP) threshold (3 microV isoresponse criterion) at 8kHz stimulation occurred. When this criterion was reached blood and perilymph was sampled and the total platinum concentration was measured. The number of days necessary to reach criterion threshold shift varied from 6 to 22. At this time, platinum concentration was found to be slightly more than 10 times higher in whole blood and plasma than in perilymph. While a significant correlation became apparent between threshold shift and total platinum concentration in whole blood and plasma, this was not the case for threshold shift and platinum concentration in perilymph.
authors.affiliation: Hearing Research Laboratories, Department of Otorhinolaryngology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Room G 02.531, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Sepmeijer
authors.forename: Sjaak F L
authors.initials: SF
authors.lastname: Klis
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004566:Electrodes; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D010498:Perilymph / Q000378:metabolism*; D010984:Platinum / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin